Dr. Jean Dodds opens her presentation with an explanation on how animals obtain immunity. She continues it by discussing some key points on vaccine issues and their relationship to memory cell immunity. The presentation is concluded with suggested alternatives to current vaccine practices, such as titer testing.

1. UPDATE ON VACCINE ISSUES
& WSAVA GUIDELINES (2015-2017)
September 20, 2018
W. Jean Dodds, DVM
Hemopet

2. Sponsored by
• BioGal Galed Labs
• VacciCheck

3. Memory Cell Immunity
• Memory Cells are created by B and T lymphocytes that
respond to an immune stimulus. These cells replicate when
responding to an invading antigen; form clones that retain
information about each prior exposure; and thereby generate
immune memory
• The immune system thus mounts a faster and more powerful
anamnestic response when it encounters the same antigen
again – e.g. with viral exposures and vaccines
• The immune system capacity for memory generates immunity
through vaccines, but can also trigger adverse events like
autoimmune disorders and allergies/hypersensitivity

4. B-Cell Memory Immunity
• Secreted neutralizing antibodies formed by B-cell humoral immunity
are key to protection against cytopathic viruses
• These adaptive antibodies to viruses provide early
protection, independent of T-cells, and are often lifelong
• T-cell immune responses then generate humoral long-lived immune
memory, even in the absence of virus
• An efficient line of defense against re-infection occurs, backed up
by specific B- and T- reactive memory cells
• Adaptive immunity to bacteria, fungi and parasites develops
more slowly and is relatively short-lived
(Dörner and Radbruch, Immunity 27(3):384-392, 2007; Schultz et al. J Comp
Pathol 142:S102-108, 2010)

5. T-Cell Memory Immunity
• T-cells develop in the thymus and circulate through the lymphoid
organs and tissues = naïve T-cells
• Upon encountering a specific antigen(s), an adaptive immune
response occurs
• T-cells are then induced to proliferate and differentiate in order
to remove the antigen(s) = armed effector T-cells
• Effector T-cells then act upon other target cells that see the
antigen(s)
• Tissue dendritic cells, macrophages, and B-cells are capable
of activating naïve T-cells
(Janeway Jr, et al. Immunobiology, 5th Ed, Garland Science, NY, 2001)

6. Innate Immunity
• Nonspecific immunity that provides the organism’s first line of defense
• Comprises the cells and mechanisms that defend the host from
infection by other organisms; contains both B and T cells
• Recruits immune cells to sites of infection via production of chemical
factors and cytokines
• Activates complement cascade to identify bacteria, activate cells,
and promote clearance of antibody complexes and dead cells
• Identifies and removes foreign substances present in organs, tissues,
blood and lymph
• Activates the adaptive immune system through antigen presentation
• Acts as physical, mechanical and chemical barrier to infectious
agents

7. Immune Hypersensitivity
• Hypersensitivity is believed to be the cause of allergy and certain
autoimmune diseases
• Occurs when immune system responds to very low level antigen
• Hypersensitivity reactions can be divided into four types:
• Type 1 includes common immune disorders such as asthma,
allergic rhinitis (hay fever), eczema, urticaria (hives) and
anaphylaxis
• Types 2 and 3 involve autoimmune or low affinity antibodies.
T- cells play an accomplice role and Th2 cytokines promote them
• Type 4, delayed type, is caused by over-stimulation of
lymphocytes and macrophages via Th1 cytokines, resulting in
chronic inflammation and cytokine release

8. Key Points on Vaccine Issues
• Modern vaccine technology has afforded effective
protection of companion animals against serious
infectious diseases
• But, this advancement brings increased risk of adverse
reactions (vaccinosis)
• Some are serious, chronically debilitating and even fatal
• Must balance this benefit : risk equation
• “ Be wise and immunize, but immunize wisely ! ” (Dr.
Ron Schultz)

9. Benefits of Vaccines
• More lives saved, more animal production safeguarded than
any other medical advance
• Eradicated smallpox, & nearly all polio and measles in people
• First vaccines were against small pox, anthrax, and canine
distemper
• Significantly reduced endemics of canine distemper, hepatitis
and parvovirus, but not in wildlife reservoirs
• Significantly reduced endemic feline panleukopenia
• Eliminated rabies in Europe; eradicated Rhinderpest in Africa,
foot & mouth disease in Europe

10. Vaccines & Population (Herd) Health
• To protect the population (herd) = 70 % immunized with
“core” vaccines …… but …..
• Dog population = only about 50% immunized
• Cat population = only about 25% immunized
• Best “vaccine” = natural exposure, but about 50% of
susceptible puppies or kittens will die of the disease
• Vaccine non-responders and low-responders = genetic trait

11. Vaccines & Immune
Memory Cell Immunity
• Vaccination may not equate to immunization
• But, vaccinated and truly immunized animals should be fully
protected from disease
• Immune memory cell immunity should persist life long
• Giving boosters to immunized animals is unwise, as it will introduce
unnecessary antigen, adjuvant and preservatives

12. Sterilizing Immunity =
• An immune response that completely prevents and eliminates an
infection
• Animals properly immunized against the clinically important viral
diseases have sterilizing immunity that not only prevents clinical
disease but also prevents infection. Only the presence of antibody
can prevent infection
• An animal with a positive serum antibody test is protected from
infection
• Vaccinating that animal would not cause a significant increase in
antibody titer, but hypersensitivity to vaccine components (e.g. fetal
bovine serum) may develop
• Furthermore, the animal doesn't need to be revaccinated and
should not be revaccinated since the vaccine could cause an
adverse reaction (hypersensitivity disorder)

13. Sterilizing Immunity (cont’d)
• But, not all vaccines produce sterilizing immunity
• Those that do include: distemper virus, adenovirus, and parvovirus in
the dog, and panleukopenia virus in the cat.
• Examples of vaccines that produce non-sterile immunity would be
leptospirosis, bordetella, canine influenza, rabies virus, and
herpesvirus and calicivirus --- the upper respiratory viruses of cats
• While non-sterile immunity may not protect the animal from infection,
it should keep the infection from progressing to severe clinical
disease

14. Summary on Vaccine Policy
❖AAHA 2003 – Current knowledge supports the
statement that •••
“ No vaccine is always safe, no vaccine is
always protective and no vaccine is always
indicated”
• “Misunderstanding, misinformation and the conservative
nature of our profession have largely slowed adoption of
protocols advocating decreased frequency of vaccination”

15. Summary on Vaccine Policy
❖ WSAVA 2015-2017
From Prof. Michael J. Day •••
• “Vaccination should be just one part of a holistic preventive
healthcare program for pets that is most simply delivered within
the framework of an annual health check consultation.”
• “Vaccination is an act of veterinary science that should be
considered as individualized medicine, tailored for the needs of
the individual pet, and delivered as one part of a preventive
medicine program in an annual health check visit.”

16. Vaccine Adjuvants
• Act to accelerate, prolong, or enhance antigen-specific immune
responses
• Added into vaccines to enhance their immunogenicity, but this
increases risk of autoimmune and inflammatory adverse events
following vaccination
• Killed, inactivated vaccines containing adjuvants make up about
15% of veterinary biologicals used, but have been associated with
85% of the post-vaccination reactions
• Adjuvants have been used safely in human and veterinary
medicine for decades, but there is increasing worldwide concern
about the safety of using thimerosal (mercury) and aluminum

17. Vaccine Adjuvants (cont’d)
• Simultaneous administration of even 2-3 adjuvants can overcome
genetic resistance to autoimmunity
• Impact the central nervous system by changing gene expression,
impairing brain development and immune function
• Especially of concern for children and young animals
• Potent adjuvants produce a more sustained humoral immune
response and compete favorably with the longer protection typically
afforded by MLV products
• Ringworm and chlamydia vaccines introduced for cats touted as
having the safety advantage of a killed product
• But, no killed combination vaccine product is now available for dogs

18. Vaccine Non-Responders
• Genetic trait ; do not breed them
• They will remain susceptible to the disease life long
• Rate = 1:1000 for CPV (parvovirus)
- Especially Black Labradors and Akitas
• Rate = 1: 5000 for CDV (distemper virus)
- Especially Greyhounds
• Rate = zero for CAV (hepatitis, adenovirus)
• Rate = unknown for cats

20. Adverse Vaccine Events = Vaccinosis
• How and Why do they occur ?
• Millions of people, pets and livestock vaccinated annually
• Reactions relatively rare --- about 3-5 events per 100 vaccines
given
• Affects those genetically predisposed
• Can be acute, sub-acute and delayed for 30-45 days
• New data relates vaccinosis to integrity and function of gut
microbiome

21. Etiology of Autoimmune Diseases
Stress
Sex
Hormones
Genetics Virus

22. Autoimmune Diseases
Autoimmunity:
• Develops in genetically susceptible individuals
• May be triggered by environmental agents operating by
nonspecific inflammation and/or molecular mimicry
• Is the result of the sum of genetic and environmental
factors that override normal mechanisms of self-
tolerance; and
• Is most often mediated by T cells or is characterized by
an underlying dysfunction in T cells.
(Sinha et al. Science, 248, 1380-1388, 1990)

23. Adverse Reactions & Cautions
Canine Distemper Virus
• Rate = 1:100,000 for Rockborn & Snyder Hill vaccine strains
• Rockborn strain CDV found in most of today’s MLV vaccines
• Produces PVE = post-vaccinal encephalitis, blindness & death
• Recombinant (rCDV) Recombitek (Merial) cannot cause PVE
• Rate = 1: 500,000 for Onderstepoort strain , but less potent
• When MLV CDV combined with adenovirus (Hepatitis) in combo ,
risk of immune suppression and PVE increases– especially in puppies

24. ASIA Syndrome - Adjuvant-Induced
Autoimmunity
• Mercury-induced inflammation causes autoimmunity, including
thyroiditis, multiple sclerosis, immune-complex kidney diseases,
chronic fatigue syndrome and myalgia
• Immunomodulation and allergic, delayed-type hypersensitivity are
reported and can manifest as contact dermatitis and other signs
• Mercury is still widely used in dental fillings, therapy of syphilis, and as
the preservative thimerosal in rabies and other vaccines
• Nickel, gold, silver, aluminum, and chromium may function similarly
• Endocrine status and chronic infections are predisposing factors
• Genetic predisposition is involved in animals and likely in people
(Stejskal, IMAJ 15:714-715, 2013; Shoenfeld et al. J Autoimmun 36:4-8, 2011)

25. Maternal Immunity & Protection
Milk Replacer
• Feeding milk replacer proteins instead of natural colostrum will
coat bowel of newborns and shut down absorption of
antibodies needed for protection from disease
• Give FFP (Fresh-Frozen Plasma) immediately to orphan or weak
pups to get passive immunity ; then add milk replacer
Vaccine Timing
• Last puppy vaccine at 16-18 weeks for protection
• Last kitten vaccine at 12-14 weeks for protection

26. Vaccination, Exposure & Protection
CDV (distemper virus)
• Vaccinates immediately protected, if exposed simultaneously
• MLV CDV does not shed appreciably
CPV (parvovirus)
• Vaccinates protected after 48-72 hrs; exposed pups get sick
• MLV CPV sheds from post-vaccine days 3-14; exposure risk
• Shed vaccine CPV not seen on Idexx SNAP, but present on CPV
PCR of feces for 2 weeks

27. Kennel Cough & Flu Vaccines
• Oral /Intranasal Bordetella releases interferon, which
impairs growth of other respiratory viruses (parainfluenza,
adenovirus - 2, influenza)
• Injectable Bordetella vaccine does not release interferon
• Hypersensitivity reactions with intranasal vaccine
• Kennel cough vaccines not 100% effective . Needed ?
• Influenza (vaccine needed? )
• Produces fever whereas kennel cough does not. When
combined with Streptococcus, 2-3% can die

28. More on Canine Influenza
Best way to clinically distinguish canine influenza from
kennel cough:
• Kennel Cough typically does not produce a fever unless it subsequently
leads to pneumonia in debilitated dogs
• Canine Flu usually presents as a fever with a cough in the early stages.
For mild fever (102-103 o F) no treatment is needed. If above 104 o F, then
secondary pneumonia can result and should be treated promptly with
antibiotics and supportive care.
• We do not routinely give canine influenza vaccines to healthy pups or
adult dogs.
• Even though canine flu viruses (H3N2 and H3N8) are highly contagious

29. Anamnestic Immune Response

30. Vaccine Dosage
Body Mass
• Same dose intended for toy and giant breeds
• Why ?
• MLV vaccines --immunogenic principle not based on body mass
• Killed inactivated vaccines -- should be adjusted for body mass
• Minimum/optimum doses for protection ?
• Excess antigen present

31. • Small breed adult dogs, between 3-9 years of age, were studied.
• Dogs were healthy and had no vaccines for at least 3 years.
• Purpose was to determine if just half-dose of bivalent CDV & CPV
vaccine elicited protective serum antibody titer responses.
• Titer levels compared 1 & 6 months later vs pre-vaccine titers.
• Half-dose vaccine resulted in sustained protective serum antibody
titers for all dogs studied.
Half-Dose CDV & CPV Vaccine Study
in Small Breed Adult Dogs
W. Jean Dodds, DVM [JAHVMA, vol. 41; 12-21, winter 2015]

32. Vaccine Dosage (cont’d)
Age
• Optimal age for response
12 wks + for puppies
10 wks for kittens
Same for all breeds and sizes?
• Earliest age for safety
6 wks for puppies and kittens
• Effective age varies
• Blocking effects of maternal immunity

33. Hormonal State During Vaccination
Avoid Vaccination
•Period just before estrus (30 days)
•During estrus
•Pregnancy
•Lactation

34. Periodicity of Booster Vaccinations
• No evidence that annual boosters are necessary
• Need to lengthen interval
(every 3-7 years or more for healthy adults)
• Geriatric animals vaccinated only with caution
• Monitor serum antibody titers instead

35. Alternatives to Current Vaccine
Practices
• Measure serum antibody titers
• Avoid unnecessary vaccines or over-vaccinating
• Caution vaccinating sick or febrile animals
• Tailor specific minimal vaccine protocol for dogs/cats breeds or
families at risk for adverse reactions
• Start vaccination series later (9-10 wks, dog; 8 wks cat)
• Alert caregiver to watch puppy/kitten behavior and health
after boosters
• Avoid revaccination of those with prior adverse events

36. Vaccine Titer (Serum Antibody) Testing
• Assesses the immunologic status of animals against common,
clinically important infectious diseases
• Determines if vaccine boosters are required or advisable
• Once animal’s titer stabilizes it should remain constant for many years
• Protection is indicated by a positive titer result
• Any measurable antibody level shows protection
• Titers sustained unless animal has medical problem such as cancer or
receives high/prolonged doses of immunosuppressive drugs
• Viral vaccines prompt an immune response that lasts much longer
than that elicited by classic antigen
• Clinicians often do not distinguish between these two kinds of
responses

37. Vaccine Titer Testing (cont’d)
• Determines whether an individual animal responded to a vaccine
• Determines if an individual vaccine is effectively immunizing animals
• Negative result usually means titer has failed to reach the threshold
of providing sterile immunity
• Negative titer not the same as a zero titer and may not mean that
animal is unprotected
• Important distinction, because a negative or zero antibody titer for
the “core” vaccines indicates the animal is not protected against
canine parvovirus and may not be protected against canine
distemper virus or feline panleukopenia virus
• Published studies show that 90-98% of properly vaccinated dogs
and cats have good measurable titers

38. Factors Affecting Vaccine Response
Core Vaccines
• Adult dogs (n=1031; both sexes and those 2-18 yrs old were
vaccinated with MLV CDV, CPV, CAV-2)
• Serum antibody titers were measured 11-13 months later
• Adequate titers were present in 86% (CPV), 72% (CDV) and 71%
(CAV-2)
• No titer differences were seen between sexes
• Titers to CPV higher in young dogs, higher to CDV in older dogs,
but CAV-2 titers did not change with age
(Taguchi et al. Can Vet J 52:983-986, 2011; ibid Microbiol Immunol 56:579-582,
2012)

39. Factors Affecting Vaccine Response
Rabies
• Serum rabies titers were run on 18,339 dogs and cats in the UK
• Choice of vaccine, period between vaccine and testing, sex
and age of the animal , and country of origin were assessed
• For dogs - all factors affected failure rate (titer below 0.5
IU/mL)
except sex
• For cats – all factors had a significant effect on titerlevels
(Mansfield et al. Vet Rec 154:423-426, 2004; Kennedy et al. Vaccine 25(51):
8500-8507, 2007; Jakel et al. Dev Biol (Basel) 131:431-437, 2008; Minke et al.
Vet Microbiol 133 (3):283-286, 2009; Berndtsson et al. Acta Vet Scan 53(1):22-
32, 2011)

40. The Thimerosal (Mercury)-Free
Rabies Vaccine

41. Rabies Challenge Study Update
• Rabies remains a serious and usually fatal disease in
many countries, despite the absence in North America
of documented cases of rabies in vaccinated, truly
immunized dogs and cats for 2 decades
• While most pet dogs are vaccinated for rabies, fewer
cats have historically been vaccinated until recent laws
have required it
• The Rabies Challenge Fund research studies are now at
years 7 and 8; the initial live rabies challenge phase
results showed > 85% survival at 5 years

42. Available Vaccine Titers for Dogs
• Distemper Virus
• Parvovirus
• Adenovirus 2 (hepatitis)
• Bordetella
• Leptospirosis
• Lyme disease
• Corona Virus [not recommended]
• Rabies Virus (RFFIT: for export or non-export)

43. Available Vaccine Titers for Cats
• Panleukopenia Virus
• Herpes Virus (Rhinotracheitis Virus)
• Calicivirus
• Rabies Virus (RFFIT: for export or non-export)

44. Available Vaccine Titers for Horses
• Equine Herpes (EHV –1, and – 4) (rhino)
• Equine Encephalitis (EEE, WEE, VEE)
• Equine Influenza
• Equine Viral Arteritis
• Potomac Horse Fever
• Rabies Virus (RFFIT: export or non-export)
• West Nile Virus Antibody Titer

45. Options & Solutions
Education, Education, Education
• Understand duration of vaccinal immunity
• Accept potential for adverse events
• Recognize adverse events rather than dismiss or deny them
• Inform clients of issues and encourage options
• Offer titers for ‘core’ vaccines triennially/more often
• Explain optional vaccines may not be needed

46. Vaccine Conclusions for Canines*
Factors increasing risk of adverse events 3 days
after vaccination:
• Young adult age
• Small-breed size
• Neutering
• Multiple vaccines given per visit
• These risks should be communicated to clients
_______________________________________________
* from Moore et al, JAVMA 227:1102–1108, 2005

47. Vaccine Conclusions for Felines*
Factors that increase risk of adverse events 30
days after vaccination:
• Young adult age
• Neutering
• Multiple vaccines given per visit
• These risks should be communicated to clients, and the
number of vaccines administered concurrently limited
___________________________________________________
*from Moore et al, JAVMA 231:94-100, 2007

48. • Veterinary practitioners are confronting increasing
numbers of patients exhibiting signs of immunologic
dysfunction and disease
• Onset typically occurs within 30-45 days of vaccination
• Evidence implicates vaccines and their adjuvants as
potential triggering agents combined with genetic
predisposition of the vaccinated host
• Number of adjuvants used in veterinary vaccines should
be re-examined
Conclusions

49. • Discovery and implementation of new types of vehicles
that enhance immune response to vaccines should be
encouraged
• Multifaceted approach is needed to recognize the
situation, develop alternative strategies for containing
infectious disease, and reduce the environmental impact
of conventional vaccines
• To begin, periodicity between adult booster vaccinations
can be increased to three or more years with monitoring
of serum antibody levels (to assess protection against the
clinically important infectious agents)
Conclusions (cont’d)

50. Footprints in the Sand